Despite improvements in sanitation and water supply, cholera remains a serious public health burden. Vaccination is included among recommendations for cholera control. Cultural concepts of illness are likely to affect vaccine acceptance. This study examined social and cultural determinants of anticipated acceptance of an oral cholera vaccine (OCV) prior to a mass vaccination campaign in Zanzibar. Using a cultural epidemiological approach, 356 unaffected adult residents were studied with vignette-based semi-structured interviews. Anticipated acceptance was high for a free OCV (94%), but declined with increasing price. Logistic regression models examined social and cultural determinants of anticipated acceptance at low (USD 0.9), medium (USD 4.5) and high (USD 9) price. Models including somatic symptoms (low and high price), social impact (low and medium) and perceived causes (medium and high) explained anticipated OCV acceptance better than models containing only socio-demographic characteristics. Identifying thirst with cholera was positively associated with anticipated acceptance of the low-priced OCV, but acknowledging the value of home-based rehydration was negatively associated. Concern about spreading the infection to others was positively associated at low price among rural respondents. Confidence in the health system response to cholera outbreaks was negatively associated at medium price among peri-urban respondents. Identifying witchcraft as cause of cholera was negatively associated at medium and high price. Anticipated acceptance of free OCVs is nearly universal in cholera-endemic areas of Zanzibar; pre-intervention assessments of community demand for OCV should not only consider the social epidemiology, but also examine local socio-cultural features of cholera-like illness that explain vaccine acceptance.